How to manage a 56-year-old female with type 2 diabetes mellitus, presenting with intermittent abdominal pain, hyperglycemia, and elevated liver enzymes, on a background of complex medical and social history?

Management of Type 2 Diabetes with Hyperglycemia, Abdominal Pain, and Elevated Liver Enzymes

This patient requires immediate insulin therapy due to A1C of 9.6% (>9%), along with urgent evaluation for diabetic ketoacidosis given her history of DKA, current hyperglycemia, abdominal pain, and laboratory abnormalities including low bicarbonate (19 mmol/L) and glucosuria (3+). 1, 2

Immediate Priority: Rule Out Diabetic Ketoacidosis

Check serum or urine ketones immediately given this patient's presentation of:

• A1C 9.6% with glucose 121 mg/dL (suggesting recent severe hyperglycemia) 1
• Abdominal pain (classic DKA symptom) 1
• Low bicarbonate (19 mmol/L, normal 20-29) suggesting metabolic acidosis 1
• 3+ glucosuria with polyuria/polydipsia 1
• History of prior DKA 1

The combination of abdominal pain, hyperglycemia, and low bicarbonate in a patient with prior DKA history is DKA until proven otherwise. 1 Abdominal pain occurs in DKA and can be confused with primary abdominal pathology. 3, 4

Insulin Initiation is Mandatory

Start basal insulin immediately because:

• A1C 9.6% is >9%, which mandates insulin therapy per guidelines 1, 2
• Home glucose readings 160-240 mg/dL indicate persistent severe hyperglycemia 1
• Patient discontinued Mounjaro 3 months ago and is on Jardiance monotherapy, which is inadequate 1

Begin with basal insulin (long-acting analogue preferred over NPH to reduce hypoglycemia risk), starting at 10 units daily or 0.1-0.2 units/kg/day, titrating every 2-3 days based on fasting glucose to target 90-130 mg/dL. 1

Restart or Add GLP-1 Receptor Agonist

Once ketones are negative and patient is stabilized, restart a GLP-1 RA (such as Mounjaro/tirzepatide or alternative if cost-prohibitive) before further insulin intensification. 1

• GLP-1 RAs should be considered before insulin intensification in all patients without contraindications 1
• The dual GIP/GLP-1 RA tirzepatide has very high efficacy for glucose lowering 1
• When adding GLP-1 RA to insulin, reassess and likely reduce insulin dose to prevent hypoglycemia 1
• Address cost barriers: work with patient and social services to access patient assistance programs or consider lower-cost alternatives 1

Add or Restart Metformin

Initiate metformin 500 mg daily with gradual titration to 2000 mg daily in divided doses (if not already taking it): 2, 5

• Her eGFR is 103 mL/min/1.73m², so no contraindication exists 2
• Start low dose to minimize GI side effects, increase by 500 mg every 1-2 weeks 1, 2
• Metformin can be continued with insulin therapy for ongoing metabolic benefits 1
• Monitor vitamin B12 levels periodically given her diabetic neuropathy 2

Evaluate Elevated Liver Enzymes

The elevated AST (39 IU/L), ALT (75 IU/L), and alkaline phosphatase (143 IU/L) likely represent glycogenic hepatopathy from poor glycemic control rather than primary liver disease. 6, 7

• Glycogenic hepatopathy occurs in poorly controlled diabetes (both type 1 and 2) with intermittent hyperglycemia/hypoglycemia and excessive insulin use 6, 7
• Presents with hepatomegaly, abdominal pain, and mildly-to-moderately elevated aminotransferases 6, 7
• Liver synthetic function remains normal (her albumin 4.2 g/dL is normal) 6, 7
• This condition is completely reversible with sustained euglycemic control 6, 7
• Liver biopsy is not needed if clinical picture fits and enzymes improve with glycemic control 6
• Differentiate from NAFLD: glycogenic hepatopathy improves with better diabetes control, while NAFLD relates to insulin resistance and obesity 4, 7

Address the Abdominal Pain

The abdominal pain has three possible etiologies that must be considered:

1. DKA-related abdominal pain (most urgent): Check ketones immediately 1, 3
2. Glycogenic hepatopathy: Hepatomegaly from glycogen accumulation causes RUQ pain and early satiety 6, 7
3. Diabetic gastroparesis: Given her diabetic neuropathy, gastroparesis is possible, manifesting as bloating, early satiety, and abdominal pain 4

The urinalysis showing 6-10 WBCs (slightly elevated) is likely not clinically significant given negative nitrites, negative leukocyte esterase, and absence of urinary symptoms. 1

Optimize Jardiance Use

Continue Jardiance (SGLT2 inhibitor) for its cardiovascular and renal protective benefits, but with important caveats: 1

• SGLT2 inhibitors can precipitate euglycemic DKA, especially during illness or fasting 1
• Educate patient to check ketones during illness, even if glucose is not severely elevated 1
• Temporarily discontinue during acute illness or if ketones are present 1

Monitoring and Follow-up

• Recheck A1C in 3 months to assess response to intensified therapy 1, 2
• Monitor liver enzymes monthly initially; expect normalization with improved glycemic control 6, 7
• Check fasting glucose daily and adjust insulin dose every 2-3 days until target 90-130 mg/dL achieved 1
• Consider continuous glucose monitoring (CGM) if affordable, given her prior use of Libre and need for intensive monitoring 1
• Reassess need for mealtime insulin if A1C remains >7% despite optimized basal insulin (>0.5 units/kg/day suggests overbasalization) 1

Address Psychosocial Factors

Provide or continue counseling support given: 1

• Depression on fluoxetine for 3 years 1
• Significant social stressors (relative's dementia, vision loss, caregiver burden) 1
• These factors directly impact diabetes self-management and glycemic control 1

Common Pitfalls to Avoid

• Do not delay insulin initiation when A1C >9%; this represents clinical inertia and prolongs complications risk 1, 2
• Do not assume abdominal pain is benign without ruling out DKA in a patient with prior DKA history 1
• Do not perform invasive liver evaluation (biopsy) before optimizing glycemic control, as glycogenic hepatopathy resolves with euglycemia 6, 7
• Do not discontinue SGLT2 inhibitor permanently due to DKA concern; instead, educate on ketone monitoring during illness 1
• Do not start insulin at full dose; begin conservatively and titrate to avoid hypoglycemia 1